Allergic rhinitis is a symptomatic disorder of the nose caused by exposure to allergens, which induce an IgE mediated inflammation of the membranes lining the nose. Typical symptoms of allergic rhinitis include running nose, sneezing, nasal blockage and itchy nose. In addition, allergic rhinitis is often associated with asthma and is a risk factor for developing asthma. Pruritus or itch is defined as an unpleasant sensation of the skin that provokes the urge to scratch. It is a characteristic feature of many skin diseases like urticaria. Urticaria is a kind of skin rash notable for pale red, raised itchy bumps which is frequently caused by allergic reactions.
Antihistamines are common first-line treatment for the symptoms of allergic rhinitis by blocking the action of histamine, a chemical released by the immune system in allergic reactions. Antihistamines that bind to the histamine 1 receptor (H1) serve as important therapeutic agents to counter the effects of histamine in the skin. H1 antihistamines have been proven to be effective at reversing the pruritus and cutaneous lesions of chronic urticaria.
Bepotastine (+)-(S)-4-[4-[(4-Chlorophenyl)(2-pyridyl)methoxyl]piperidinol]butyric acid is an anti-allergic having an antihistamine action. Bepotastine was disclosed in U.S. Pat. No. 4,929,618. Bepotastine is a non-sedative selective antagonist of H1-histamine receptor and exhibits control of eosinophil migration into inflamed tissues. The half life of Bepotastine is 2.4±0.1 hour.
Bepotastine besilate is commercially available as Talion film coated immediate release tablets 5 mg and 10 mg and as Talion orally disintegrating tablets 5 mg and 10 mg in Japan.
The dosing regimen recommended for Bepotastine requires twice daily administration in order to maintain a constant therapeutic level of Bepotastine. Twice daily administration of the immediate release dosage of Bepotastine results in peak-trough profile due to short half life and rapid elimination of the drug. High systemic exposure (Cmax) of the drug may result in systemic side-effects.
Controlled release pharmaceutical compositions offer many advantages over immediate-release pharmaceutical compositions. Apart from increasing the patient compliance by decreasing the frequency of administration, the controlled release pharmaceutical compositions maintain effective blood levels for longer period of time and causes reduction in systemic drug exposure related side effects.
U.S. Pat. No. 6,692,769 discloses sustained release particles comprising a drug containing core coated with a mixed coating of a hydrophobic organic compound-water insoluble polymer and a preparation method of tablets using these sustained release particles.
U.S. Pat. No. 6,638,534 discloses unit dose composition capable of releasing a medicinal substance at a targeted site in the intestine. The composition comprises a core material containing a medicinal substance coated with a mixed film of hydrophobic organic compound and enteric polymer.
Due to short half-life in vivo, Bepotastine and its pharmaceutically acceptable salts as currently formulated are commonly administered twice daily. It has been observed, surprisingly that it is possible to modify the release profile of Bepotastine Besilate, obtaining a controlled release of Bepotastine up to 16 hours.
The controlled release pharmaceutical compositions of Bepotastine are administered less frequently and may alleviate the above disclosed problems associated with conventional immediate release compositions.
The specification discloses oral controlled release pharmaceutical compositions of Bepotastine or pharmaceutically acceptable salts thereof. The oral controlled release pharmaceutical compositions of the invention provide release of Bepotastine in a controlled manner over a prolonged or extended period of time. The oral controlled release pharmaceutical compositions of the invention are substantially bioequivalent to two immediate release tablets of Bepotastine. Such pharmaceutical compositions also offer the advantage of once-a-day dosing of Bepotastine, increased patient compliance, ease of manufacturing, high throughput of manufacturing and easy scale-up, etc.